Nanopore sequencing: a newbie’s perspective on needs in a clinical setting | LC 25

Biography

Marcel Nelen earned his bachelor's in Biochemistry from the University of Applied Sciences in Oss and worked as a technician before moving to the University of Florida (Gainesville) for two years. After returning to the Netherlands, he pursued a PhD in Nijmegen studying Cowden's disease. He later explored repeat expansion diseases and DNA repair during his postdoc. Marcel then trained as a laboratory specialist in clinical genetics at UMC Utrecht. After four years, he returned to Radboudumc to head the next-generation sequencing core facility, gaining extensive experience with sequencing technologies. In 2022, he accepted the proposition to become the head of the Genome Diagnostics laboratory at UMC Utrecht.

Abstract

In September 2024, UMC Utrecht and Oxford Nanopore Technologies began a collaboration to explore the capabilities of long-read nanopore sequencing and evaluate whether the PromethION platform could become a key tool for whole-genome sequencing (WGS) in our laboratory.

While the clinical laboratory has extensive experience with short-read sequencing (Illumina, NovaSeq X+), it has limited exposure to long-read sequencing. The goal of the initial phase was to gain hands-on experience, during which we dedicated significant time to developing a simple and robust workflow capable of routinely producing 15–20 kb fragments after DNA shearing.

Once this was achieved, we progressed to the next phase, which involved generating sufficient sequencing data for a 30× long-read WGS in a single run, without the need for washing or reloading the nanopore flow cells.

We have now reached a point where we are confident in moving forward with the main goal of the collaboration: to routinely test the platform in our genomic diagnostics using a cohort of samples with various mutations, covering all types of genetic variants.